Project Summary/Abstract HIV-infected (HIV+) patients are living longer in the context of an unprecedented rise in the use of prescription opioids for the treatment of pain and a concurrent epidemic of NMUPO. HIV+ individuals are disproportionately impacted by pain, depression, post-traumatic stress disorder and substance use, increasing their risk for non- medical use of prescription opioids (NMUPO: use of prescription opioids without a prescription or simply for the experience or feeling the drugs cause) and its associated harms. This is especially true among HIV+ patients who are also veterans. Existing literature regarding NMUPO among HIV+ individuals is limited as it is drawn from non-generalizable populations; was collected in earlier HIV treatment eras; and relies on cross-sectional designs or limited long-term follow-up. Further, data regarding the role of modifiable factors (i.e. prescription opioids and benzodiazepines) on NMUPO and its consequences are sparse. Understanding NMUPO patterns over time, factors contributing to escalating NMUPO, and its associated impact on health outcomes is critical to designing interventions improve health outcomes in HIV+ veterans. Therefore, our aims are to use existing longitudinal data on >2800 HIV+ individuals in the Veterans Aging Cohort Study (VACS) to characterize: 1) important trajectories of NMUPO such as escalation of use, 2) the association between NMUPO trajectories and HIV-related outcomes, and 3) the association between NMUPO trajectories and mortality. VACS data will allow us to examine these aims among a cohort of HIV+ patients receiving care through nine Veterans Affairs Infectious Disease clinics across the United States. Since 2005, VACS has collected three survey waves of self-reported measures including NMUPO using items from the National Survey on Drug Use and Health, pain, depressive symptoms, and other substance use. These self-report data will be supplemented by detailed information available through the electronic medical record, including prescriptions (e.g. opioids and benzodiazepines), medical and psychiatric diagnoses (i.e. PTSD), and laboratory data. HIV-related outcomes include VACS Index score, a validated composite biomarker derived from routine labs that is a measure of overall HIV disease severity and accurately predicts mortality; detectable viral load and retention in HIV care. The innovative aspects of this research include its focus on patients who are engaged in routine medical care in the VA (i.e. the largest single provider of HIV in the United States), the ability to evaluate NMUPO and simultaneous detailed prescription opioid information (including duration, dose, formulation) and benzodiazepines, and a longitudinal analytic approach that incorporates dual-outcome trajectory models to evaluate NMUPO trajectories and their impact on important health outcomes, including the VACS Index and mortality. This work, conducted by a multidisciplinary team with expertise in observational and intervention research, will provide essential data to inform the development of future screening and treatment strategies to mitigate risks and prevent harm of NMUPO and prescribed medications among HIV+ patients.